Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Oct;10(10):778-783.
doi: 10.1111/1753-0407.12794. Epub 2018 Jul 2.

Quantitative path to deep phenotyping: Possible importance of reduced hepatic insulin degradation to type 2 diabetes mellitus pathogenesis

Richard N Bergman  1 , Francesca Piccinini  1 , Isaac Asare Bediako  1 , Morvarid Kabir  1 , Cathryn Kolka  1 , David Polidori  2 , Marilyn Ader  1
Affiliations

Quantitative path to deep phenotyping: Possible importance of reduced hepatic insulin degradation to type 2 diabetes mellitus pathogenesis

Richard N Bergman et al. J Diabetes. 2018 Oct.

Abstract

Diabetes is often thought of as one of two diseases: Type 1 diabetes (T1D), which is caused by immunological destruction of the beta-cells, and Type 2 diabetes (T2D), which is due to a combination of insulin resistance and relative failure of the beta-cells to compensate for the resistance. It is becoming clear, however, that even within these two definitions there may be considerable heterogeneity (1). There are several approaches to examine heterogeneity of T2D. Among these approaches are the use of biomarkers to categorize the disease, or the examination of variants in the genome. A third approach – the one we have been using in our laboratory – is to identify specific phenotypes which may contribute to failure to regulate the glucose level. We have identified a small group of such phenotypes which can be distinguished and measured using clinical protocols and/or mathematical modeling.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Hyperbolic law of glucose tolerance. Bergman and colleagues hypothesized that in normal individuals the product of insulin secretion and insulin sensitivity is a constant called Disposition Index (DI). This suggests that environmental reduction in insulin sensitivity, such as induced by obesity, pregnancy or puberty, will be countered with an increase in insulin secretion, thus preventing impairment of glucose tolerance.
Figure 2.
Figure 2.
We are hypothesizing that, at least in some ethnic groups, reduced extraction of insulin by the liver (i.e., reduced degradation) might be a causal factor in the pathogenesis of Type 2 diabetes. (A) The normal nondiabetic individuals insulin is secreted by the beta-cells, and enters the liver directly, wherein half is degraded, and half reaches the systemic circulation to regulate glucose utilization and adipose tissue ipolysis. (B) In some patients at risk for Type 2 diabetes, liver insulin degradation has been shown to be suppressed (e.g., in African Americans). Thus, a larger fraction of the secreted insulin reaches the systemic circulation. Hyperinsulinemia may then result in insulin resistance at muscle, stressing the beta-cells, and at adipose tissue, resulting in lipolysis and inappropriately increased endogenous glucose production.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ahlqvist E, Storm P, Käräjämäki A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol 2018;S22113-587(18)30051-2. [Epub ahead of print] - PubMed
    1. Himsworth HP The mechanism of diabetes mellitus III. Lancet 1939;ii:153–157.
    1. Reaven GM, Olefsky JM Relationship between heterogeneity of insulin responses and insulin resistance in normal subjects and patients with chemical diabetes. Diabetologia 1977;13(3):201–6. - PubMed
    1. Andres R, Swerdloff R, Pozefsky T, et al. Manual feedback technique for the control of blood glucose concentration In Automation in Analytical Chemistry, edited by Skeggs LT Jr. New York: Mediad; 1966;486–491.
    1. DeFronzo RA, Tobin JD, Andres R Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979;237(3):E214–23. - PubMed
  NODES
Association 1
twitter 2